Abstract

Roscovitine (Rosc) and purvalanol (Pur) are competitive inhibitors of cyclin-dependent kinases (CDKs) by targeting their ATP-binding pockets. Both drugs are shown to be effective to decrease cell viability and dysregulate the ratio of pro- and anti-apoptotic Bcl-2 family members, which finally led to apoptotic cell death in different cancer cell lines in vitro. It was well established that Bcl-2 family members have distinct roles in the regulation of other cellular processes such as endoplasmic reticulum (ER) stress. The induction of ER stress has been shown to play critical role in cell death/survival decision via autophagy or apoptosis. In this study, our aim was to investigate the molecular targets of CDK inhibitors on ER stress mechanism related to distinct cell death types in time-dependent manner in HeLa cervical cancer cells. Our results showed that Rosc and Pur decreased the cell viability, cell growth and colony formation, induced ER stress-mediated autophagy or apoptosis in time-dependent manner. Thus, we conclude that exposure of cells to CDK inhibitors induces unfolded protein response and ER stress leading to autophagy and apoptosis processes in HeLa cervical cancer cells.

Notes

Acknowledgements

This study was supported by Istanbul Kultur University Scientific Projects Support Center and TUBITAK (The Scientific and Technological Research Council of Turkey) 2209 Program. The team was Gozde Sukur, Bahar Sarıkaya, Kubra Tugtekin and Ezgi Gultekin. We are thankful for technical assistance to Gozde Sukur, Kubra Tugtekin and Ezgi Gultekin for Figs. 1a, b and 3b, c. Pelin Ozfiliz-Kilbas and Bahar Sarıkaya were involved in all figures. The data obtained by Benan Temizci was repeated by Bahar Sarıkaya. The project was designed by Elif Damla Arisan and Narcin Palavan-Unsal. Ajda Coker-Gurkan and Pınar Obakan-Yerlikaya interpreted the data and were involved in the writing of the manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical statement

We declare that this article does not involve any studies with human participants or animals performed by any of the authors. The research has been performed on commercially available cell lines. All authors read and confirmed the final version of the manuscript.